Immunogenic nano-phthalocyanine enables oxygen-economic photodynamic therapy for hepatocellular carcinoma

Hepatocellular carcinoma (HCC), the primary form of liver cancer, is associated with a poor 5-year survival rate, underscoring the urgent need for novel therapeutic strategies. Photodynamic therapy (PDT) is a promising cancer treatment modality that employs reactive oxygen species (ROS) to induce tumor cell death while stimulating anti-tumor immune responses through damage-associated molecular patterns (DAMPs) released by dying cells. However, conventional photosensitizers are hindered by their low ROS production efficiency and high oxygen dependency, which limit their efficacy against hypoxic solid tumors. To address these limitations, we synthesized axially substituted bis[3-(N-morpholinyl)propoxy] phthalocyaninato silicon (SiPc), which self-assembles into nanoparticles capable of generating ROS via a hypoxia-tolerant type-I mechanism. SiPc nanoparticles (SiPcNPs) have demonstrated potent cytotoxicity against cancer cells at low concentrations. Furthermore, SiPcNP-mediated PDT promotes dendritic cell maturation in vitro and enhances CD8 + T cell infiltration in vivo . These findings suggest that SiPcNPs are potential candidates for overcoming microenvironmental resistance in PDT, with dual mechanisms of direct tumor eradication and immune potentiation, thereby providing a foundation for clinical translation in HCC management.